[en] Teleost fish such as zebrafish (Danio rerio) are increasingly used for physiological, genetic
and developmental studies. Our understanding of the physiological consequences of altered
gravity in an entire organism is still incomplete. We used altered gravity and drug treatment
experiments to evaluate their effects specifically on bone formation and more generally on
whole genome gene expression. By combining morphometric tools with an objective scoring
system for the state of development for each element in the head skeleton and specific gene
expression analysis, we confirmed and characterized in detail the decrease or increase of bone
formation caused by a 5 day treatment (from 5dpf to 10 dpf) of, respectively parathyroid
hormone (PTH) or vitamin D3 (VitD3). Microarray transcriptome analysis after 24 hours
treatment reveals a general effect on physiology upon VitD3 treatment, while PTH causes
more specifically developmental effects. Hypergravity (3g from 5dpf to 9 dpf) exposure
results in a significantly larger head and a significant increase in bone formation for a subset
of the cranial bones. Gene expression analysis after 24 hrs at 3g revealed differential
expression of genes involved in the development and function of the skeletal, muscular,
nervous, endocrine and cardiovascular systems. Finally, we propose a novel type of
experimental approach, the "Reduced Gravity Paradigm", by keeping the developing larvae at
3g hypergravity for the first 5 days before returning them to 1g for one additional day. 5 days
exposure to 3g during these early stages also caused increased bone formation, while gene
expression analysis revealed a central network of regulatory genes (hes5, sox10, lgals3bp,
egr1, edn1, fos, fosb, klf2, gadd45ba and socs3a) whose expression was consistently affected
by the transition from hyper- to normal gravity.